ID SIK2_MOUSE Reviewed; 931 AA. AC Q8CFH6; DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2003, sequence version 1. DT 05-OCT-2016, entry version 114. DE RecName: Full=Serine/threonine-protein kinase SIK2; DE EC=2.7.11.1; DE AltName: Full=Salt-inducible kinase 2; DE Short=SIK-2; DE AltName: Full=Serine/threonine-protein kinase SNF1-like kinase 2; GN Name=Sik2; Synonyms=Snf1lk2; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] {ECO:0000305, ECO:0000312|EMBL:BAC53845.1} RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, AND MUTAGENESIS OF LYS-49. RC TISSUE=Adipose tissue {ECO:0000312|EMBL:BAC53845.1}; RX PubMed=12624099; DOI=10.1074/jbc.M211770200; RA Horike N., Takemori H., Katoh Y., Doi J., Min L., Asano T., Sun X.J., RA Yamamoto H., Kasayama S., Muraoka M., Nonaka Y., Okamoto M.; RT "Adipose-specific expression, phosphorylation of Ser794 in insulin RT receptor substrate-1, and activation in diabetic animals of salt- RT inducible kinase-2."; RL J. Biol. Chem. 278:18440-18447(2003). RN [2] RP FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-175 AND SER-587, RP AND MUTAGENESIS OF LYS-49 AND THR-175. RX PubMed=16817901; DOI=10.1111/j.1742-4658.2006.05291.x; RA Katoh Y., Takemori H., Lin X.-Z., Tamura M., Muraoka M., Satoh T., RA Tsuchiya Y., Min L., Doi J., Miyauchi A., Witters L.A., Nakamura H., RA Okamoto M.; RT "Silencing the constitutive active transcription factor CREB by the RT LKB1-SIK signaling cascade."; RL FEBS J. 273:2730-2748(2006). RN [3] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-532; SER-534 AND RP SER-587, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, and RC Spleen; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and RT expression."; RL Cell 143:1174-1189(2010). CC -!- FUNCTION: Phosphorylates 'Ser-789' of IRS1 in insulin-stimulated CC adipocytes, potentially modulating the efficiency of insulin CC signal transduction. Inhibits CREB activity by phosphorylating and CC repressing TORCs, the CREB-specific coactivators. CC {ECO:0000269|PubMed:12624099, ECO:0000269|PubMed:16817901}. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC {ECO:0000269|PubMed:12624099}. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:12624099}; CC -!- ENZYME REGULATION: Activated by phosphorylation on Thr-175. CC {ECO:0000250}. CC -!- SUBUNIT: Interacts with and phosphorylates TORC2/CRTC2. CC {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12624099}. CC -!- TISSUE SPECIFICITY: Present in both white and brown adipose CC tissues with levels increasing during adipocyte differentiation. CC Lower levels observed in the testis. CC {ECO:0000269|PubMed:12624099}. CC -!- PTM: Phosphorylated at Thr-175 by STK11/LKB1 in complex with CC STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. CC {ECO:0000250}. CC -!- PTM: Acetylation at Lys-53 inhibits kinase activity. Deacetylated CC by HDAC6 (By similarity). {ECO:0000250}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK CC Ser/Thr protein kinase family. SNF1 subfamily. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- SIMILARITY: Contains 1 UBA domain. {ECO:0000255|PROSITE- CC ProRule:PRU00212}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB067780; BAC53845.1; -; mRNA. DR CCDS; CCDS40627.1; -. DR RefSeq; NP_848825.2; NM_178710.3. DR UniGene; Mm.104932; -. DR UniGene; Mm.439989; -. DR ProteinModelPortal; Q8CFH6; -. DR SMR; Q8CFH6; 12-337, 16-306. DR BioGrid; 231647; 1. DR DIP; DIP-60734N; -. DR STRING; 10090.ENSMUSP00000038761; -. DR iPTMnet; Q8CFH6; -. DR PhosphoSite; Q8CFH6; -. DR MaxQB; Q8CFH6; -. DR PaxDb; Q8CFH6; -. DR PRIDE; Q8CFH6; -. DR DNASU; 235344; -. DR GeneID; 235344; -. DR KEGG; mmu:235344; -. DR CTD; 23235; -. DR MGI; MGI:2445031; Sik2. DR eggNOG; KOG0586; Eukaryota. DR eggNOG; ENOG410XNQ0; LUCA. DR HOGENOM; HOG000048716; -. DR InParanoid; Q8CFH6; -. DR KO; K16311; -. DR PhylomeDB; Q8CFH6; -. DR PRO; PR:Q8CFH6; -. DR Proteomes; UP000000589; Unplaced. DR CleanEx; MM_SNF1LK2; -. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA:MGI. DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0046626; P:regulation of insulin receptor signaling pathway; IDA:UniProtKB. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR InterPro; IPR017090; Ser/Thr_kinase_SIK1/2. DR InterPro; IPR015940; UBA. DR Pfam; PF00069; Pkinase; 1. DR PIRSF; PIRSF037014; Ser/Thr_PK_SNF1-like; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; SSF56112; 2. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR PROSITE; PS50030; UBA; 1. PE 1: Evidence at protein level; KW Acetylation; ATP-binding; Complete proteome; Cytoplasm; Kinase; KW Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Serine/threonine-protein kinase; Transferase. FT CHAIN 1 931 Serine/threonine-protein kinase SIK2. FT /FTId=PRO_0000086663. FT DOMAIN 20 271 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT DOMAIN 295 335 UBA. {ECO:0000255|PROSITE- FT ProRule:PRU00212}. FT NP_BIND 26 34 ATP. {ECO:0000250|UniProtKB:Q13131, FT ECO:0000255|PROSITE-ProRule:PRU00159}. FT ACT_SITE 142 142 Proton acceptor. FT {ECO:0000250|UniProtKB:Q13131, FT ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027}. FT BINDING 49 49 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159, FT ECO:0000269|PubMed:12624099}. FT MOD_RES 25 25 Phosphothreonine. FT {ECO:0000250|UniProtKB:Q9H0K1}. FT MOD_RES 53 53 N6-acetyllysine; by EP300. {ECO:0000250}. FT MOD_RES 175 175 Phosphothreonine. FT {ECO:0000250|UniProtKB:Q9H0K1}. FT MOD_RES 532 532 Phosphoserine. FT {ECO:0000244|PubMed:21183079}. FT MOD_RES 534 534 Phosphoserine. FT {ECO:0000244|PubMed:21183079}. FT MOD_RES 587 587 Phosphoserine. FT {ECO:0000244|PubMed:21183079}. FT MUTAGEN 49 49 K->M: Loss of kinase activity. FT {ECO:0000269|PubMed:12624099, FT ECO:0000269|PubMed:16817901}. FT MUTAGEN 175 175 T->E: Low levels of constitutive FT activity. {ECO:0000269|PubMed:16817901}. SQ SEQUENCE 931 AA; 104198 MW; 5CF2FB8DCDC689F4 CRC64; MVMADGPRHL QRGPVRVGFY DIEGTLGKGN FAVVKLGRHR TTKTEVAIKI IDKSQLDAVN LEKIYREVQI MKMLDHPHII KLYQVMETKS MLYLVTEYAK NGEIFDYLAN HGRLNESEAR RKFWQILSAV DYCHGRKVVH RDLKAENLLL DNNMNIKIAD FGFGNFFKTG ELLATWCGSP PYAAPEVFEG QQYEGPQLDI WSMGVVLYVL VCGALPFDGP TLPILRQRVL EGRFRIPYFM SEDCEHLIRR MLVLDPSKRL SIAQIKEHKW MLIEVPVQRP ILYPQEQENE PSIGEFNEQV LRLMHSLGID QQKTVESLQN KSYNHFAAIY FLLVERLKSH RSSFPVEQRL DGRQRRPSTI AEQTVAKAQT VGLPVTLHPP NVRLMRSTLL PQASNVEAFS FPTSSCQAEA AFMEEECVDT PKVNGCLLDP VPPVLVRKGC QSLPSSMMET SIDEGLETEG EAEEDPSQAF EAFQATRSGQ RRHTLSEVTN QLVVMPGAGK MFSMSDNPSL ESVDSEYDMG SAQRDLNFLE DSPSLKDIML ANQPSPRMTS PFISLRPANP AMQALSSQKR EAHNRSPVSF REGRRASDTS LTQGIVAFRQ HLQNLARTKG ILELNKVQLL YEQMGSNADP TLTSTAPQLQ DLSSSCPQEE ISQQQESVSS LSASMHPQLS PQQSLETQYL QHRLQKPNLL PKAQSPCPVY CKEPPRSLEQ QLQEHRLQQK RLFLQKQSQL QAYFNQMQIA ESSYPGPSQQ LALPHQETPL TSQQPPSFSL TQALSPVLEP SSEQMQFSSF LSQYPEMQLQ PLPSTPGPRA PPPLPSQLQQ HQQPPPPPPP PPPQQPGAAP TSLQFSYQTC ELPSTTSSVP NYPASCHYPV DGAQQSNLTG ADCPRSSGLQ DTASSYDPLA LSELPGLFDC EMVEAVDPQH NGVVSCLARE T //